This document discusses drug stability and factors that affect it. It defines drug stability as a drug product remaining within established specifications for identity, strength, quality and purity. Factors like temperature, humidity, light and microbial contamination can cause drug degradation through chemical, physical and biological processes like hydrolysis, oxidation and photolysis. The document outlines various packaging materials and how they can impact stability. It also describes different types of stability studies conducted, including long-term real-time testing and accelerated methods like elevated temperature to evaluate products' shelf lives under normal conditions.

1. Drug stability
Under the guidance of RAMESH
BABU.J
M.Pharm,Sr.assiatant professor
By
WILWIN

2. CONTENTS
1) Definition
2) Adverse effects of drug instability
3) Factors affecting drug stability
4) Types of drug degradation
5) Types of stability studies
6) Methods of accelerated stability testing in
dosage forms
7) Temperature and humidity control

3. Drug stabilty:It is the capacity of a drug product to remain with in
specifications established to ensure its identity ,strength ,quality
and purity.
Adverse effects of instability of drugs
 Loss of active drug (e.g. aspirin hydrolysis, oxidation of
adrenaline).
 Loss of vehicle (e.g. evaporation of water from o/w creams,
evaporation of alcohol from alcoholic mixtures).
 Loss of content uniformity (e.g. creaming of emulsions, impaction
of suspensions).
 Loss of elegance (e.g. fading of tablets and coloured solutions).
 Reduction in bioavailability (e.g. ageing of tablets resulting in a
change in dissolution profile).
 Production of potential toxic materials (e.g. breakdown products
from drug degradation).

4. Factors Affecting Stability
Environmental
factors
Microbial
contamination
Containers and
closure

5. Environmental factors
Temperature
light
Moisture

6. Temperature
 3 types of storage temperatures
1.room temperature
2.cold temperature
3.Freeze storage
1.Room temperature:
 Upto 30/25o c
2.Cold temperature/Refrigerator storage:
 Upto 2-8o c
3.Freeze storage:
 Storage between -20 to -10o c

7. Light(photolysis)
 the shorter the wavelength more the energy is
absorbed per mole
It means: decomposition by light
 Various sources of light are sunlight, metal
halide lamps, fluorescent lamps, or other indoor
lighting sources.
 These reactions can be induced by exposure to
photolysis sources emitting in the 290–800 nm
region.

8.  Relationship between wavelength and
associated energy of various forms of light.
Type of
Wavelength
radiation:
board outers
U.V.
Visible
I.r.
Energy
Kcal mol-1
50 – 400
400 – 750
750 – 10,000
287 – 72
36 - 1

9. Photolysis is prevented by:
 Suitable packing in amber couloured bottles
 Card board outers
 Aluminum foil wrappers
MOISTURE
 It enhances the hydrolytic degradation
 Packing materials such as Glass and Plastic are
usually chosen to prevent exposure of drug
product to high humid conditions

10. Microbial Instability
Sources of microbial contamination
Water
gram-negative groups:
Pseudomonas,
Xanthamonas,
Flavobacterium
Air
Mould spores: Penicillium,
Aspergillus
Bacterial spores: Bacillus
spp. Yeasts
Raw materials
Starches
Pigments
Micrococci
Coliforms
Salmonella

11. Sources of Microbial
Contamination
Gums
Animal products
Actinomyces
Salmonella, Coliforms
Personnel
Coliforms,
Staphylococci,
Sterptococci

12. Packaging And Stability
1.Glass
 Glass is resistant to chemical and
physical change and is the most commonly used
material.
Limitations
1. Its alkaline surface
Overcome
use of Borosilicate glass
2. Ions may precipitate
the use of buffers
insoluble crystals from the
glass
3- Permits the transmission
of light which may
accelerate decomposition.
Amber coloured glass

13. Packing and Stability
2.PLASTICS
The problems with plastic are:
 Migration of the drug through the plastic into the
environment.
 Transfer of environmental moisture, oxygen, and
other elements into the pharmaceutical product.
 Leaching of container ingredients into the drug.
 Adsorption of the active drug or
excipients by the plastic.

14. Packing and Stability
3.Metals
 Various alloys and aluminum tubes may be utilized
as containers for emulsions, ointments, creams and
pastes.
 Limitation:
They
may
cause
corrosion
and
precipitation in the drug product.
 Overcome: Coating the tubes with polymers may
reduce these tendencies.

15. Packing and Stability
Rubber
 Rubber also has the problems of extraction of drug
ingredients and leaching of container ingredients.
 The
pretreatment
of
rubber
vial
stoppers
and
closures with water and steam reduces potential
leaching.

16. Types of degradations
Chemical
Physical
Biological

17. Chemical Degradation
1- Hydrolysis:
Hydrolysis means “splitting by water’’

18. Some functional groups subject
to Hydrolysis
Drug type
Examples
Esters
Aspirin, alkaloids
Dexmethasne sodium phosphate
Nitroglycerin
Lactones
Pilocarpine
Spironolactone
Amides
Chloramphenicol
Imides
Glutethimide
Malonic ureas
Barbiturates

19. Chemical Stability
2- Oxidation
Oxidation of inorganic and organic
compounds is explained by a loss of
electrons and the loss of a molecule of
hydrogen.
3-Photolysis

20. Physical Stability
Physical stability implies that:
 The formulation is totally unchanged throughout its
shelf life and has not suffered any changes by way of
appearance,
organoleptic
brittleness, particle size etc.
 It is significant as it affects:
1.pharmaceutical elegance
2.drug content uniformity
3.drug release rate.
properties,
hardness,

21. Physical Stability
Formulation
Likely physical
instability problems
Oral solutions 1- Loss of flavor
2- Change in taste
3- Presence of off
flavors due to
interaction with
plastic bottle
4- Loss of dye
5- Precipitation
6- discoloration
Effects
Change in
smell or feel
or taste

22. Formulation
Parenteral
solutions
Likely physical
instability
problems
1. Discoloration due to
photo chemical
reaction or
oxidation
2. Presence of
precipitate due to
interaction with
container or
stopper
3. Presence of
“whiskers”
4. Clouds due to:
(i) Chemical changes
(ii) The original
preparation of a
supersaturated
Effects
Change in
appearance and in
bio-availability

23. Physical stability
Formulation
Suspensions
Likely physical
instability
problems
1- settling
2- caking
3- crystal
growth
Effects
1-Loss of drug
content
uniformity in
different doses
from the
bottle
2- loss of
elegance.

24. Physical stability
Formulation
Emulsions
Likely physical
Effects
instability
problems
1- Creaming
1- Loss of drug
2- coalescence content
uniformity in
different doses
from the
bottle
2- loss of
elegance

25. Physical stability

26. Physical stability
Formulation
Semisolids
(Ointments and
suppositories)
Likely physical
Effects
instability
problems
1. Changes in:
1-Loss of drug
a) Particle size content
uniformity
b) Consistency
2. Caking or
coalescence
2- loss of
elegance
3. Bleeding
3-change in
drug release
rate.

27. Physical stability
Formulation
Tablets
Likely physical
instability
problems
Effects
Change in:
Change in
drug release
a) Disintegration
time
b) Dissolution
profile
c) Hardness
d) Appearance (soft
and ugly or
become very
hard)

28. Physical stability
Formulation
Capsules
Likely physical
instability
problems
Change in:
a) Appearance
b) Dissolution
c) Strength
Effects
Change in drug
release

29. Types of Stability Studies
1.Long-Term (Real-Time) Stability Testing
 Stability evaluation of the physical, chemical,
biological and microbiological characteristics of
a drug product
 duration of the shelf life

30. Accelerated stability Testing
 Studies designed to increase the rate of chemical
degradation or physical change(s) of a drug product
by using exaggerated storage conditions with the
purpose of monitoring degradation reactions.
 To evaluate the impact of short term excursions and
predicting
the
shelf-life
under
normal
storage
studies may
include
conditions.
 The design
of
accelerated
elevated temperature, high humidity and intense
light.

31. Methods Of Accelerated
Stability Testing In Dosage
forms
 Freeze Thaw test
 Centrifugal Test
 Shaking test
 Elevated Temperature test

32. Temperature and humidity
control
General storage conditions
study
Storage Conditions
Minimum Time Period
at Submission
Long term
25 ± 2°C / 60% RH ± 5%
Zone I,II.
30 ± 2°C / 35% RH ± 5%
Zone III.
30 ± 2°C / 60% RH ± 5%
Zone IV.
6 Months
6 Months
6 Months
Intermediate
30 ± 2°C / 60% RH ± 5%
6 Months
Accelerated
40 ± 2°C / 75 % RH ± 5%
6 Months

33. Products packed in semipermeable containers.
Study
Storage Conditions
Minimum Time Period
at Submission
Long term
25 ± 2°C / 40% RH ± 5%
zone I,II
6 Months
Long term
30 ± 2 ºC/ 60% RH ± 5%
zone III,IV
6 Months
Intermediate
30 ± 2°C / 60% RH ± 5%
6 Months
Accelerated
40 ± 2°C / NMT 25% RH
6 Months

34. Products intended for
storage in a Refrigerator
Study
Storage Conditions
Minimum Time Period
at Submission
Long term
5 ± 3°C
6 Months
Accelerated
25 ± 2°C / 60% RH ± 5%
6 Months

35. Products intended for
storage in a freezer
Study
Storage Conditions
Minimum Time Period
at Submission
Long term
-20 ± 5°C
12 Months